Keratoconus and mascular and granular corneal dystrophies are potentially blinding diseases. It is believed that disturbances in connective tissues such as collagen and proteoglycans cause these diseases. A direct relationship between the disease processes and these macromolecules, however, still remains unexplained. Since elucidation is a prerequisite for eventual developments in all clinical aspects, we therefore, propose to investigate the biosynthesis, metabolism and structure of collagen and proteoglycans in diseased and scarred corneas and compare them with those of normal controls. With both the tissue culture and organ culture approaches, we will determine the amount and types of collagen and proteoglycan synthesized. In addition, we will examine the messenger RNAs responsible for synthesizing these molecules. It is our hope to understand the connective tissue synthesis in corneas at a molecular level and to detect and define specific biochemical abnormalities. Our eventual goal is to apply the information obtained to the clinical care of these corneal diseases.